Evidence from patients with Alzheimer's disease suggests that the basal forebrain cholinergic system plays an important role in memory. In support of this proposal, we have found impaired visual recognition memory in macaques with lesions of the major nuclei of this system. We have also found that recognition memory in normal monkeys can be improved by administration of the cholinesterase inhibitor physostigmine and impaired by the cholinergic muscarinic-receptor blocker scopolamine. Another form of retention, spatial memory, has also been found to be impaired by scopolamine, although it may be more resistant to such an effect than is recognition memory. In addition, our results indicate that scopolamine acts at a very early stage, suggesting an effect on primary, rather than secondary memory. Based on previous results indicating that THC may be exerting its effects through an action on the limbic system we administered this drug to monkeys performing an automated recognition memory task. Doses of THC that we previously found to affect recognition memory in the Wisconsin General Testing Apparatus produced impairments in performance, but only at delays exceeding 30 seconds. This is in contrast to the impairment produced by scopolamine, where the maximal effect was observed with delays of less than 3 seconds. These results suggest that THC is exerting its effects on recognition memory through a system other than the cholinergic system. In a series of experiments on habit formation, we administered the dopaminergic-neurotoxin MPTP to monkeys, which produced learning and motor impairments that resolved within a few weeks. In spite of the recovery, the animals were more sensitive to the effects of scopolamine, suggesting residual damage to the dopaminergic system. Two years after the last dose of MPTP was given, substantial dopamine deficits were confirmed in these animals by positron emission tomography. The animals were subsequently shown to be impaired in learning a detour reaching task and a spatial memory task. In vivo dialysis showed dopamine levels in these monkeys were reduced in the prefrontal cortex, caudate nucleus, and putamen compared to the same areas in normal control monkeys.